Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Jun;84(6):795-813.
doi: 10.1016/j.jinf.2022.04.018. Epub 2022 Apr 9.

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial

Xinxue Liu  1 , Alasdair P S Munro  2 , Shuo Feng  3 , Leila Janani  4 , Parvinder K Aley  5 , Gavin Babbage  6 , David Baxter  7 , Marcin Bula  8 , Katrina Cathie  2 , Krishna Chatterjee  9 , Wanwisa Dejnirattisai  10 , Kate Dodd  8 , Yvanne Enever  11 , Ehsaan Qureshi  12 , Anna L Goodman  13 , Christopher A Green  12 , Linda Harndahl  14 , John Haughney  15 , Alexander Hicks  14 , Agatha A van der Klaauw  16 , Jonathan Kwok  17 , Vincenzo Libri  18 , Martin J Llewelyn  19 , Alastair C McGregor  20 , Angela M Minassian  21 , Patrick Moore  22 , Mehmood Mughal  7 , Yama F Mujadidi  23 , Kyra Holliday  24 , Orod Osanlou  25 , Rostam Osanlou  26 , Daniel R Owens  2 , Mihaela Pacurar  2 , Adrian Palfreeman  27 , Daniel Pan  27 , Tommy Rampling  18 , Karen Regan  28 , Stephen Saich  6 , Teona Serafimova  29 , Dinesh Saralaya  28 , Gavin R Screaton  10 , Sunil Sharma  19 , Ray Sheridan  30 , Ann Sturdy  20 , Piyada Supasa  10 , Emma C Thomson  31 , Shirley Todd  30 , Chris Twelves  24 , Robert C Read  2 , Sue Charlton  32 , Bassam Hallis  32 , Mary Ramsay  33 , Nick Andrews  33 , Teresa Lambe  3 , Jonathan S Nguyen-Van-Tam  34 , Victoria Cornelius  4 , Matthew D Snape  5 , Saul N Faust  35 ; COV-BOOST study group
Affiliations
Clinical Trial

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial

Xinxue Liu et al. J Infect. 2022 Jun.

Erratum in

Abstract

Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters.

Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.

Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30-94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461-10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74-0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.

Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

Keywords: COVID-19 vaccine; Fractional dose; Heterologous boost; Homologous boost; Immunogenicity; Persistence; Third dose.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest KC acts on behalf of University Hospital Southampton as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Janssen, Medimmune, Merck, Pfizer, Sanofi and Valneva. She receives no personal financial payment for this work. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an Investigator and/or providing consultative advice on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vaccine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck and Valneva vaccines and antimicrobials. He receives no personal financial payment for this work. ALG is named as an inventor on a patent covering use of a particular promoter construct that is often used in ChAdOx1-vectored vaccines and is incorporated in the ChAdOx1 nCoV-19 vaccine. ALG may benefit from royalty income paid to the University of Oxford from sales of this vaccine by AstraZeneca and its sublicensees under the University's revenue sharing policy. JH has received payments for presentations for AstraZeneca, Boehringer Ingelheim, Chiesi, Ciple & Teva. VL acts on behalf of University College London Hospitals NHS Foundation Trust as an Investigator on clinical trials of COVID-19 vaccines funded or sponsored by vaccine manufacturers including Pfizer, AstraZeneca and Valneva. He receives no personal financial payment for this work. PM acts on behalf of University Hospital Southampton NHS Foundation Trust and The Adam Practice as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Novavax, Medicago and Sanofi. He received no personal financial payment for this work. JSN-V-T is seconded to the Department of Health and Social Care, England until 31st March 2022. MR has provided post marketing surveillance reports on vaccines for Pfizer and GSK for which a cost recover charge is made. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax. Janssen, Medimmune and MCM vaccines. He received no personal financial payment for this work.

Figures

Fig 1
Fig. 1
Consort diagram.
Fig 2
Fig. 2
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with ChAD/ ChAD.
Fig 2
Fig. 2
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with ChAD/ ChAD.
Fig 2
Fig. 2
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with ChAD/ ChAD.
Fig 2
Fig. 2
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with ChAD/ ChAD.
Fig 3
Fig. 3
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with BNT/ BNT.
Fig 3
Fig. 3
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with BNT/ BNT.
Fig 3
Fig. 3
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with BNT/ BNT.
Fig 3
Fig. 3
Immunogenicity A) Anti-spike IgG (ELU/mL); B) Pseudotype virus neutralising antibody (NT50); C) Live virus neutralising antibody (NT80); D) Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population primed with BNT/ BNT.
Fig 4
Fig. 4
Anti-spike IgG (ELU/mL) at D28 and D84 amongst the SARS-CoV-2 naïve population by age group A) ChAD/ChAd, B) BNT/BNT.
Fig 4
Fig. 4
Anti-spike IgG (ELU/mL) at D28 and D84 amongst the SARS-CoV-2 naïve population by age group A) ChAD/ChAd, B) BNT/BNT.
Fig 5
Fig. 5
Pseudotype virus neutralising antibody (NT50) at D28 and D84 amongst the SARS-CoV-2 naïve population by age group A) ChAD/ChAd, B) BNT/BNT.
Fig 5
Fig. 5
Pseudotype virus neutralising antibody (NT50) at D28 and D84 amongst the SARS-CoV-2 naïve population by age group A) ChAD/ChAd, B) BNT/BNT.
Fig 6
Fig. 6
Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population by age group A) ChAD/ChAd, B) BNT/BNT.
Fig 6
Fig. 6
Cellular response (SFC per million PBMCs) at D28 and D84 amongst the SARS-CoV-2 naïve population by age group A) ChAD/ChAd, B) BNT/BNT.
Fig 7
Fig. 7
Live neutralising antibodies against wild type, Delta and Omicron at 28 days post boost.
See this image and copyright information in PMC

References

    1. OurWorldinData. COVID-19 vaccine booster doses administered per 100 people. 2021. Available from: https://ourworldindata.org/grapher/covid-vaccine-booster-doses-per-capita.
    1. Munro A.P.S., Janani L., Cornelius V., Aley P.K., Babbage G., Baxter D., et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. Lancet. 2021 - PMC - PubMed
    1. Andrews N., Stowe J., Kirsebom F., Toffa S., Sachdeva R., Gower C., et al. Effectiveness of COVID-19 booster vaccines against covid-19 related symptoms, hospitalisation and death in England. Nat Med. 2022 - PMC - PubMed
    1. Lyngse F.P., Kirkeby C.T., Denwood M., Christiansen L.E., Mølbak K., Møller C.H., et al. Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: evidence from Danish Households. medRxiv. 2022: 2022.01.28. 22270044.
    1. Cameroni E., Bowen J.E., Rosen L.E., Saliba C., Zepeda S.K., Culap K., et al. Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift. Nature. 2021 - PMC - PubMed

Publication types